Process for preparing carotenoid polyene chain compounds and intermediates for preparing the same

ABSTRACT

The present invention provides an intermediate compound used for synthesis of polyene chain structure, that is an important moiety of carotenoid compounds, a process for preparing the same, and carotenoid polyene chain compounds prepared by using the intermediate, and, in particular, a process for preparing lycopene. The process for preparing the carotenoid polyene chain compound employs an allylic sulfone compound as starting material, which is reacted with C-5 sulfide compound to extend the carbon chain. The resultant thio-sulfone compound is oxidized, and the obtained disulfone compound is combined with C-10 di(haloallylic) sulfide compound to form a chain compound containing the desired number of carbon atoms. Then, the diallylic sulfone obtained by oxidation of the diallylic sulfide is subjected to Ramberg-Baklund reaction in order to form the central triene bond. After removal of sulfonyl groups, carotenoid polyene chain compound is obtained.

TECHNICAL FIELD

[0001] The present invention relates to a process for preparingcarotenoid polyene chain compounds. More specifically, it relates tointermediate compounds which are useful for synthesis of carotenoidcompounds having polyene chain structure, and a process for preparingthe same, and a process for preparing polyene chain compounds,especially lycopene, by using the intermediate compound.

BACKGROUND ART

[0002] Carotenoid compounds have polyene chain structure. Specificexamples of the compounds include beta-carotene, lycopene, astaxanthin,bixin, and the like. The carotenoid compounds have been widely used asnatural dyes, and recently, these compounds are reported to haveexcellent anti-tumor effect, by virtue of their selective reactivitywith radicals and singlet oxygen known as carcinogens. In thesecircumstances, a variety of commercial products containing carotene,including cosmetics or taste food, have been merchandised. However,there still remain conflict opinions on the anti-tumor activity ofbeta-carotene, since beta-carotene is reported to have a harmful effecton smokers or patients having lung cancer. Thus, people pay moreincreasing attention to lycopene, having stronger anti-oxidation abilitywith no conflict opinion on the anti-tumor activity.

[0003] To meet such a tendency, the requirement of developing a processfor effectively synthesizing polyene chain structures that constructlycopene also increases.

[0004] In the meanwhile, the most representative conventional syntheticprocess for preparing lycopene was developed by Isler; that is a processfor synthesizing polyene chain on the basis of Wittig reaction (ReactionScheme 1; Helv. Chim. Acta 1956, 39, 463-473).

[0005] According to Reaction Scheme 1, C-10 dialdehyde compound issubsequently reacted with vinyl ether and propenyl ether compound toform a continuously conjugated carbon chain wherein each C-2 unit andC-3 unit was respectively added to the aldehyde groups of C-10dialdehyde compound. Throughout the stage, C-10 unit has been added tothe dialdehyde to form C-20 dialdehyde, of which the triple bond at thecenter of the molecule was then partially reduced to give crocetin.

[0006] Then, crocetin thus obtained is subjected to Wittig Reaction withWittig salts to form lycopene. The Wittig salts used in this stage iswhat was prepared as a result of reaction of geranyl bromide withtriphenylphosphine.

[0007] However, the synthetic process for lycopene according to ReactionScheme 1 includes many reaction stages to carry out in order to formcrocetin, and the synthetic efficiency is low owing to the trouble intreating phosphine oxide as the by-product obtained as a result ofWittig Reaction.

[0008] Another synthetic process for synthesizing lycopene is developedby Karrer. The process is based on coupling reaction by using alkynylanion, partial hydrogenation and dehydration. The synthetic process isillustrated in Reaction Scheme 2 (Helv. Chim. Acta 1950, 33, 1349-1352).

[0009] According to Reaction Scheme 2, an anion obtained by addingmetallic zinc to propargylic bromide is subjected to coupling reactionwith Ψ-ionone, to give C-16 intermediate. Then, two molecules of thealkynyl anion obtained by adding bases to the C-16 intermediate werecoupled with C-8 diketone compound to form forwards containing 40 carbonatoms required for synthesis of lycopene. The partial hydrogenation ofthe two triple bonds and dehydration of the forward compound providelycopene.

[0010] The synthetic process for lycopene according to Reaction Scheme 2is relatively simple, however, it is not easy to form a double bondhaving trans configuration.

[0011] Thus, the first technical object of the present invention is toprovide an allylic sulfide, that is, a C-5 compound usable for chainextension to effectively synthesize polyene chain structure describedabove.

[0012] Another technical object of the present invention is to provide aprocess for extending the carbon chain by the use of said allylicsulfide.

[0013] Still another object of the present invention is to provide aprocess for preparing polyene chain compounds, especially lycopene, byusing said process for extending carbon chain.

DISCLOSURE OF THE INVENTION

[0014] In order to achieve the first technical object, the presentinvention provides allylic sulfides represented by Chemical Formula 1:

[0015] Chemical Formula 1

[0016] Wherein, X is selected from the group consisting of —Cl, —Br, —I,—OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph represents phenylgroup.

[0017] The second technical object of the present invention is achievedby a process for preparing an allylic sulfide of Chemical Formula 1,which comprises the steps of (a-1) oxidizing isoprene to obtain isoprenemonoxide, (b-1) reacting the isoprene monoxide with benzene thiol toobtain 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A); and (c-1)reacting the compound (A) with a halogenating compound or sulfonylatingcompound.

[0018] In the formulas, X is selected from the group consisting of —Cl,—Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph representsphenyl group.

[0019] The third technical object of the present invention is achievedby a process for extending carbon chain by the use of allylic sulfide ofChemical Formula 1, which comprises the steps of (a-2) deprotonatingallylic sulfone compound (B), and reacting the resultant compound withallylic sulfide of Chemical Formula 1 to obtain thio-sulfone compound(C); and (b-2) selectively oxidizing the thio-sulfone compound (C) toobtain the corresponding allylic sulfone compound (D).

[0020] In the formulas, R is selected from the group consisting ofhydrogen, C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN,—COOR′ (wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selectedfrom the group consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph,—OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph represents phenyl group.

[0021] The fourth technical object of the present invention is achievedby a process for preparing a carotenoid polyene chain compoundrepresented by Chemical formula 2, which comprises the steps of (a-3)deprotonating the allylic disulfone compound (D), and reacting theresultant compound with not more than 0.5 equivalent of diallylicsulfide (E) (wherein, Y is a halogen atom) on the basis of 1 equivalentof allylic disulfone compound (D) to obtain allylic sulfide compound(F); (b-3) selectively oxidizing the allylic sulfide compound (F) toobtain allylic sulfone compound (G); (c-3) subjecting the allylicsulfone compound (G) to Ramberg-Baklund reaction to givetetra(phenylsulfonyl)-triene compound (H); and (d-3) reacting thecompound (H) with a base. If R of Chemical Formula 2 is prenyl, theprocess provides lycopene.

[0022] In the formulas, R is selected from the group consisting ofhydrogen, C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN,—COOR′ (wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, Y is selectedfrom the group consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph,—OSO₂C6H₄CH₃ and —OSO₂CH₃, and Ph represents phenyl group.

[0023] In the process for preparing an allylic sulfide of ChemicalFormula 1, the ring opening of isoprene monoxide of stage (b-1) ispreferably performed by using Cu(I)-containing salt as a catalyst, andN,N-dimethylformamide (DMF) as solvent, because the objective compoundhaving a double bond of trans configuration can be obtained as majorproduct under such reaction conditions.

[0024] In the process for extending carbon chain by the use of allylicsulfide of Chemical Formula 1, specific examples of R include methyl,ethyl and propyl group for C1˜C30 alkyl group, vinyl, allyl and prenylgroup for C1˜C30 alkenyl group, and phenyl and naphthyl group for arylgroup. X is preferably Cl or Br in terms of reactivity, while R ispreferably hydrogen or prenyl.

[0025] Further, the C-5 unit can be added as desired by repeating stage(a-2) and (b-2) one or more times by using compound (D) as the startingmaterial.

[0026] Selective oxidation of stage (b-2) can be preferably performed byadding hydrogen peroxide solution dropwise to thio-sulfone compound (C)in the presence of a metal oxide catalyst such as lithiummolybdenate-niobate (LiNbMoO₆) or vanadium oxide (V₂O₅) at roomtemperature. Selective oxidation under such reaction conditions givesexcellent yields.

[0027] In the process for preparing a carotenoid polyene chain compoundrepresented by Chemical formula 2, specific examples of R includemethyl, ethyl and propyl group for C1˜C30 alkyl group, vinyl, allyl andprenyl group for C1˜C30 alkenyl group, and phenyl and naphthyl group foraryl group. In particular, it is preferable that R is hydrogen orprenyl.

[0028] In the stage (a-3), Y of compound (E) is preferably Br in termsof reactivity, if R of allylic disulfone compound (D) is hydrogen orprenyl. Deprotonation of allylic disulfone compound (D) should beperformed by adding 2 equivalent of base to 1 equivalent of allylicdisulfone compound (D) at low temperature, preferably at a temperaturenot higher than −40° C. Specific examples of the base include n-BuLi,s-BuLi, t-BuLi, phenyl lithium, NaNH₂, lithium diisopropylamide (LDA),lithium hexamethyldisilazide, sodium hexamethyldisilazide, and the like.

[0029] Selective oxidation of stage (b-3) can be preferably performed byadding a mixture of urea-hydrogen peroxide (UHP) and phthalic anhydridedropwise to allylic disulfone compound (D) at low temperature, or addinghydrogen peroxide solution dropwise to sulfide compound (D) in thepresence of a metal oxide catalyst such as lithium molybdenate-niobate(LiNbMoO₆) or vanadium oxide (V₂O₅) at room temperature.

[0030] Ramberg-Baklund reaction of stage (c-3) is preferably carried outunder a condition excluding oxygen in the air, for example, undernitrogen or argon atmosphere in terms of reactivity and yield.

[0031] The base used in stage (d-3) is not particularly restricted.Specific examples include NaNH₂/NH₃, and metal alkoxides such asCH₃OK/CH₃OH, CH₃ONa/CH₃OH, CH₃CH₂OK/CH₃CH₂OH, CH₃CH₂ONa/CH₃CH₂OH andt-BuOK/t-BuOH. Among them, metal alkoxide is more preferably used as thebase.

[0032] The allylic sulfide of Chemical Formula 1 according to thepresent invention, which can be used as a ground material for chainextension due to the bonding with allylic sulfone compound in the courseof synthesizing a polyene chain containing compound, is synthesized asdescribed below:

[0033] Firstly, isoprene is oxidized to give isoprene monoxide. Thoughthe oxidation reaction may be carried out under a conventional oxidativereaction condition, the present invention employs the condition of usingan oxidant such as m-chloroperoxybenzoic acid (MCPBA), or of forming acorresponding halohydrin from isoprene (J. Am. Chem. Soc., 1950, 72,4608-4613) which is then reacted with a base. Among them, the latter ismore preferable as considering regio-selectivity of the two double bondsof isoprene on the electrophilic reactant.

[0034] Then, the isoprene monoxide is reacted with benzene thiol (PhSH)to provide 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A). In thereaction, it is preferable to employ Cu(I)-containing salt as acatalyst, and N,N-dimethylformamide as solvent in the aspect ofreactivity and yield. Under these reaction conditions, the reactivity ishigh so that the reaction can be performed under mild condition atambient temperature, and the reaction process itself is simple and easyto provide economic and practical advantages. The yield is also good. Asthe Cu(I)-containing salt, any salt having Cu⁺ ion is usable, but CuCN,CuBr, CuI or CuCl is preferably used. The Cu(I)-containing salt is usedin a catalytic amount, more specifically, 0.001˜0.1 mol % of the salt ispreferably used on the basis of 1 mole of isoprene monoxide.

[0035] As a result of the above reaction, ring opening at the allylicposition of the epoxide compound is performed. In the4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) molecules thus obtained,trans configuration prevails in a trans:cis ratio of 6:1 or more.

[0036] Thereafter, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) issubjected to halogenation or sulfonylation to provide allylic sulfide ofChemical Formula 1. In this stage, halogenation of4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) may be carried out undervarious reaction conditions. For example, halogenation can be performedby employing a reaction condition of CH₃SO₂Cl/LiCl, SOCl₂, (COCl)₂,PPh₃/CCl₄, HCl, PBr₃, PPh₃/NBS or HBr. Sulfonylation may be carried outunder various conditions as well, for example under the condition ofusing a sulfonyl compound such as CF₃SO₂Cl, PhSO₂Cl, CH₃C₆H₄SO₂Cl andCH₃SO₂Cl with a base such as triethylamine (Et₃N) and pyridine (ReactionScheme 3).

[0037] In the formulas, X is selected from the group consisting of —Cl,—Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, preferably from—Cl and —Br.

[0038] Now, the reaction of ring opening at the allylic position of theisoprene monoxide is described in detail.

[0039] The ring opening reaction of isoprene monoxide may be carried outunder the conditions other than the reaction condition used in thepresent invention. Specific reaction conditions and the productdistribution under each condition are shown in Table 1 below. In Table1, Entry 5 corresponds to the reaction by using Cu(I)-containing saltand benzenethiol according to the present invention, while Entries 1 to3 to the reaction of isoprene monoxide under basic condition, andEntries 4 and 6 to the reaction under acidic condition. The ratios ofcis:trans double bond in 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A)are determined by using gas chromatography and ¹H-NMR. TABLE 1

Product ratio Yield (A) Entry Reaction Condition (%) (I) (J) (cis:trans)1 Et₃N, PhSH in MeOH, 99 96  3 1 0° C.˜room temperature, 6 Hr 2 NaH,PhSH in THF, 96 98 — 2 0° C.˜room temperature, 6 Hr 3 n-BuLi, PhSH inTHF, 100 100  — — −78° C.˜room temperature, 6 Hr 4 LiClO₄, PhSH in DMF,44 60 18 22(1:4) room temperature, 6 Hr 5 CuI(cat.), PhSH in DMF, 99 —12 87(1:6) room temperature, 6 Hr 6 AlEt₃, PhSH in benzene, 94 —  793(100:0) room temperature, 6 Hr 7 Pd(Ph₃)₄(cat.), 3 — — 100(1:9) PhSHin THF, room temperature, 6 Hr 8 Pd(OAc)₂/PPh₃(cat.), 7 — — 100(1:12)PhSH in THF, room temperature, 6 Hr

[0040] As shown in Table 1, in case of Entries 1 to 3, compound (I) wasobtained as the main product, while the desired4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was not produced at all,or was produced in an extremely small amount. In case of Entry 4,4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was synthesized at a lowyield of about 22%, and the cis:trans ratio showed relatively low transproduct (1:4) as compared to Entry 5.

[0041] In case of Entry 6 (Tetrahedron Lett. 1981, 22, 2413-2416), thedesired compound, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) couldbe obtained at a high yield of 93%, however, only to providecis-configuration of compound (A). In case of Entries 7 and 8,4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) of which transconfiguration prevails could be obtained, however, the synthetic yieldof 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was very low (3% and7%, respectively).

[0042] On the contrary, in case of Entry 5, the reaction condition ofthe present invention, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A)was obtained with an excellent yield of about 87%, and the transconfiguration prevails with cis:trans ratio of 1:6 or less. As shownabove, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) of which transconfiguration of double bond prevails could be synthesized at a highyield under the reaction condition according to the present invention.

[0043] In the meanwhile, in order to synthesize the carotenoid polyenechain compounds of Chemical Formula 2, which is represented by lycopene,the allylic sulfone compound (D) having extended carbon chain as desiredshould be firstly synthesized. As referring to Reaction Scheme 4, theprocess for preparing di(allylic sulfone) compound (D) is describedhere-in-below:

[0044] After deprotonation of the starting material, allylic sulfonecompound (B), by treating with base, allylic sulfide of Chemical Formula1 is added thereto, to obtain thio-sulfone compound (C) with 5-carbonchain extended. The specific examples of the allylic sulfone compound(B) include geranyl sulfone (R=prenyl) and prenyl sulfone (R=hydrogen).As the base, n-butyl lithium (n-BuLi) is preferably used.

[0045] The chain extension may be carried out at ambient temperature,but more preferably at a low temperature of 0° C. or lower. In case ofchain extension by using geranyl sulfone as the starting material, X ofthe compound of Chemical Formula 1 is preferably Br in terms ofreactivity.

[0046] Then, the sulfide group of thio-sulfone compound (C) isselectively oxidized to provide the corresponding allylic disulfonecompound (D). The selective oxidation is preferably carried out underthe condition of employing metal oxide such as LiNbMoO₆ or V₂O₅ as acatalyst, and hydrogen peroxide (H₂O₂) as an oxidant.

[0047] In the formulas, R is selected from the group consisting ofhydrogen, C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN,—COOR′ (wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selectedfrom the group consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph,—OSO₂C₆H₄CH₃ and —OSO₂CH₃.

[0048] When R is —CN, —COOR′ (wherein, R′ is C₁C10 alkyl group) or—C(═O)H, the corresponding compound can be prepared according toconventional processes to introduce such a functional group.

[0049] If the process for chain extension is repeated, novel allylicsulfone compounds with increased five carbon numbers can be obtainedevery time.

[0050] Now, the synthesis of carotenoid polyene chain compoundrepresented by Chemical Formula 2 according to the present invention isdescribed in detail (see Reaction Scheme 5). The process for preparingcarotenoid polyene chain compound according to the present invention isbased on the process for synthesizing beta-carotene developed by thepresent inventors (J. Org. Chem. 1999, 64, 8051-8053). It ischaracterized by using di(haloallylic) sulfide (E) in order tosynthesize C-10 triene structure of the center of the polyene chain, andapplying Ramberg-Bäklund reaction to diallylic sulfone obtained byoxidation of the sulfide compound.

[0051] In order to obtain the carbon skeletal required for carotenoids,di(haloallylic) sulfide (E) is combined with 2 equivalents or more ofallylic disulfone compound (D) based on 1 equivalent of compound (E) bymeans of Julia method (Bull. Soc. Chim. Fr., 1973, 743-750), to obtainallylic sulfide (F). The coupling reaction of di(haloallylic) sulfide(E) with allylic disulfone compound (D) is preferably carried out byadding 2 equivalents of base such as n-BuLi to allylic disulfonecompound (D) to deprotonate the compound, and then the reaction isperformed under a temperature condition of −40° C. or lower. Indi(haloallylic) sulfide (E), Y is preferably Br in terms of reactivity.

[0052] Then, only the sulfur of allylic sulfide (F) is selectivelyoxidized to give the corresponding sulfone compound (G). The selectiveoxidation reaction is preferably carried out by adding a mixture of UHPand phthalic anhydride dropwise to allylic sulfide compound (F) at a lowtemperature, or by adding H₂O₂ dropwise to the compound in the presenceof LiNbMoO₆ or V₂O₅ as a catalyst at ambient temperature. Under such areaction condition, only sulfur is selectively oxidized withoutoxidation of the double bond of allylic sulfide (F).

[0053] Thereafter, SO₂ at the center of the structure of sulfonecompound (G) is removed to form a double bond to provide compound (H).This reaction is preferably performed by treating sulfone compound (G)under Ramberg-Baklund reaction condition (J. Am. Chem. Soc., 1969, 91,7510-7512).

[0054] Lastly, four benzenesulfonyl groups are removed from compound (H)by heating the compound in the presence of alcohol solvent and alkoxidebase such as sodium alkoxide, to synthesize the polyene chain compoundof Chemical Formula 2 represented by lycopene.

[0055] In the formulas, R is selected from the group consisting ofhydrogen, C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN,—COOR′ (wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selectedfrom the group consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph,—OSO₂C₆H₄CH₃ and —OSO₂CH₃.

[0056] When the carotenoid compounds represented by lycopene areprepared according to the present invention (Example 1 to 10), thesynthetic process is simpler, easier and more efficient thanconventional processes. In addition, the problem of treating byproductssuch as phosphine oxide can be prevented according to the presentinvention. The process of the present invention is also advantageous ineasily forming the polyene chain structure having trans configuration ofdouble bond.

[0057] Allylic sulfide compound of Chemical Formula 1 according to thepresent invention is very useful for an intermediate compound to extendC5 chain, during the course of synthesis of polyene chain compound suchas lycopene.

[0058] According to the present invention, a carotenoid polyene chaincompound represented by lycopene of Chemical Formula 2 can be preparedby coupling of allylic sulfone compound (D) of the desired chain lengthand di(haloallylic) sulfide compound (E), and oxidizing the sulfide togive the corresponding diallylic sulfone compound, which is thensubjected to Ramberg-Baklund reaction, and finally eliminating thesulfonyl groups to give conjugated double bonds.

[0059] The invention is described in more detail by referring to theexamples below, but it should be noticed that the present invention isnot restricted to the examples by any means.

EXAMPLE 1: 2-Methyl-4-phenylthio-2-buten-1-ol

[0060] Isoprene monoxide (0.30 ml, 3.1 mmol) was dissolved inN,N-dimethylformamide (DMF) (7 ml), and cuprous iodide (CuI) (15 mg,0.08 mmol) and benzene thiol (PhSH) (0.33 ml, 3.2 mmol) were addedthereto at 0° C. The resultant reaction mixture was stirred at the sametemperature for about 6 hours.

[0061] When the reaction was completed, the reaction mixture was dilutedwith ether, washed with 1M-HCl three times (10 ml×3), dried overanhydrous sodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain2-methyl-4-phenylthio-2-butene-1-ol (0.52 g, 2.7 mmol) (yield: 87%).According to the analytical data of ¹H-NMR and gas chromatography, theratio of trans- to cis-double bond was not less than 6:1.

[0062]¹H-NMR: trans δ 1.56 (s,3H), 2.38 (br s, 1H),3.55 (d, 2H, J=7.7Hz), 3.92 (s, 2H), 5.54 (t, 1H, J=7.7 Hz), 7.15˜7.35 (m, 5H); cis δ 1.75(s, 3H), 2.38 (br s, 1H), 3.52 (d, 2H, J=7.9 Hz), 3.90 (s, 2H), 5.41 (t,1H, J=7.9 Hz), 7.15˜7.35 (m, 5H).

[0063]¹³C-NMR: δ 13.6, 31.5, 67.7, 119.9, 126.2, 128.9, 129.8, 136.3,139.0.

[0064] HRMS(EI) C₁₁H₁₄OS Calculated: 194.0765, Measured: 194.0771.

EXAMPLE 2: 4—Bromo-3-methyl-2-butenyl phenyl sulfide

[0065] To a solution of 2-methyl-4-phenylthio-2-butene-1-ol (23.7 g, 122mmol) dissolved in ether (80 ml), PBr₃ (16.5 g, 61 mmol) was slowlyadded at 0° C. The resultant reaction mixture was stirred at 0° C. forabout 1 hour. When the reaction was completed, the reaction mixture wasdiluted with ether, washed with distilled water, dried over anhydroussodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain 4-bromo-3-methyl-2-butenylsulfide (26.8 g, 104 mmol) (yield: 85%)

[0066]¹H-NMR: trans δ 1.64 (s, 3H), 3.51 (d, 2H, J=7.7 Hz), 3.92 (s,2H), 5.72 (t, 1H, J=7.7 Hz), 7.18˜7.41 (m, 5H); cis 6 1.85 (s, 3H), 3.56(d, 2H, J=7.9 Hz), 3.79 (s, 2H), 5.52 (t, 1H, J=7.9 Hz), 7.18˜7.41 (m,5H).

[0067]¹³C-NMR: δ 14.7, 32.4, 40.4, 125.9, 126.7, 128.9, 130.9, 135.4,135.5.

EXAMPLE 3-1: 5-Phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene

[0068] Geranyl sulfone (28.7 g, 103 mmol) was dissolved in THF (150 ml),and n-BuLi (1.6M solution in hexane/64 ml, 103 mmol) was slowly addedthereto at 0° C. The resultant mixture was stirred for 20 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (29.1 g, 113 mmol) was addedto the reaction mixture. The reaction temperature was slowly raised toroom temperature, and the mixture was stirred at the same temperaturefor about 11 hours.

[0069] To the reaction mixture, ether 100 ml was added, and theresultant mixture was subsequently washed with aqueous 1M-HCl solution(20 ml×2) and distilled water (30 ml). The mixture was dried overanhydrous sodium sulfate, and filtered.

[0070] The filtrate was concentrated by evaporation under reducedpressure, and the residue was purified by silica gel columnchromatography to obtain5-phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene (43.6g, 96 mmol) (yield: 93%).

[0071]¹H-NMR: δ 1.13 (s, 3H), 1.53 (s, 3H), 1.59 (s, 3H), 1.68 (s, 3H),1.92 (br s, 4H), 2.31 (dd, 1H, J=13.2, 11.4 Hz), 2.90 (dd, 1H, J=13.2,3.0 Hz), 3.48 (d, 2H, J=7.5 Hz), 3.87 (ddd, 1H, J=11.4, 10.3, 3.0 Hz),4.88 (d, 1H, J=10.3 Hz), 5.01 (br s, 1H), 5.32 (t, 1H, J=7.5 Hz),7.15˜7.38 (m, 5H), 7.40˜7.58 (m, 2H), 7.58˜7.70 (m, 1H), 7.75˜7.90 (m,2H).

[0072]¹³C-NMR: δ 16.0, 16.4, 17.7, 25.7, 26.2, 31.8, 37.1, 39.6, 63.2,116.8, 123.0, 123.6, 126.1, 128.7, 128.8, 129.3, 129.5, 131.9, 133.5,134.6, 136.5, 137.6, 145.6.

EXAMPLE 3-2: 5-Phenylsulfonyl-1-phenylthio-3,7-dimethyl -2,6-octadiene

[0073] Prenyl sulfone (20.2 g, 103 mmol) was dissolved in THE (100 ml),and n-BuLi (1.6M solution in hexane/72 ml, 115 mmol) was slowly addedthereto at 0° C. The resultant mixture was stirred for 20 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (25.9 g, 101 mmol) was addedto the reaction mixture. The reaction temperature was slowly raised toroom temperature, and the mixture was stirred at the same temperaturefor about 3 hours.

[0074] To the reaction mixture, ether 100 ml was added, and theresultant mixture was subsequently washed with aqueous 1M-HCl solution(20 ml×2) and distilled water (30 ml). The mixture was dried overanhydrous sodium sulfate, and filtered.

[0075] The filtrate was concentrated by evaporation under reducedpressure, and the residue was purified by silica gel columnchromatography to obtain5-phenylsulfonyl-1-phenylthio-3,7-dimethyl-2,6-octadiene (33.9 g, 87.7mmol) (yield: 91%).

[0076]¹H-NMR: δ 1.11 (s,3H), 1.52(s,3H), 1.61 (s,3H), 2.31 (dd,1H,J=13.6, 11.6 Hz), 2.86 (dd, 1H, J=13.6, 2.9 Hz), 3.48 (d, 2H, J=7.7Hz), 3.84 (ddd, 1H, J=11.6, 10.4, 2.9 Hz), 4.86 (ddd, 1H, J=10.3, 1.4,1.3 Hz), 5.31 (t, 1H, J=7.7 Hz), 7.15˜7.30 (m, 5H), 7.48˜7.53 (m, 2H),7.59˜7.61 (m, 1H), 7.80˜7.82 (m, 2H).

[0077]¹³C-NMR: δ 16.0, 17.9, 25.7, 31.8, 37.0, 63.3, 117.0, 123.1,126.1, 128.7, 128.7, 129.2, 129.6, 133.4, 134.5, 136.4, 137.7, 145.1.

EXAMPLE 4-1: 1,5-Di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene

[0078] In methyl alcohol (20 ml), dissolved was5-phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene (1.00g, 2.2 mmol), and LiNbMoO₆ (32 mg, 0.11 mmol) and H₂O₂ (30% aqueoussolution) (0.75 g, 6.6 mmol) were added thereto. The resultant reactionmixture was stirred at room temperature for about 5 hours.

[0079] When the reaction was completed, the reaction mixture wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain1,5-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (804 mg, 1.7mmol) (yield: 75%).

[0080]¹H-NMR: δ 1.15 (s, 3H), 1.36 (s, 3H), 1.58 (s, 3H), 1.67 (s, 3H),1.94 (br s, 4H), 2.33 (dd, 1H, J=13.7, 11.4 Hz), 2.93 (d, 1H, J=13.7Hz), 3.75 (d, 2H, J=8.0 Hz), 3.86 (dt, 1H, J_(d)=2.6, J_(t)=10.4 Hz),4.87 (d, 1H, J=10.4 Hz), 5.00 (s, 1H), 5.18 (t, 1H, J=8.0 Hz), 7.48˜7.58(m, 4H), 7.60˜7.69 (m, 2H), 7.78˜7.88 (m, 4H).

[0081]¹³C-NMR: δ 16.3, 16.3, 17.7,25.7,26.1,37.2, 39.7, 55.9, 63.0,113.6, 116.6, 123.5, 128.3, 128.8, 129.1, 129.3, 132.0, 133.6, 133.7,137.5, 138.8, 141.5, 146.1.

EXAMPLE 4-2: 1,5-Di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene

[0082] In methyl alcohol (80 ml), dissolved was5-phenylsulfonyl-1-phenylthio-3,7-dimethyl-2,6-octadiene (8.62 g, 22.3mmol), and LiNbMoO₆ (330 mg, 1.12 mmol) and H₂O₂ (30% aqueous solution)(7.58 g, 66.9 mmol) were added thereto. The resultant reaction mixturewas stirred at room temperature for about 11 hours.

[0083] When the reaction was completed, the reaction mixture wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain1,5-di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene (8.84 g, 21.1 mmol)(yield: 95%).

[0084]¹H-NMR: δ 1.11 (s, 3H), 1.35 (s, 3H), 1.66 (s, 3H), 2.34 (dd, 1H,J=13.8, 11.5 Hz), 2.89 (dd, 1H, J=13.8, 2.9 Hz), 3.77 (d, 2H, J=7.9 Hz),3.85 (ddd, 1H, J=11.5, 10.4, 2.9 Hz), 4.86 (d, 1H, J=10.4 Hz), 5.16 (t,1H, J=7.9 Hz), 7.51˜7.56 (m, 4H), 7.62˜7.67 (m, 2H), 7.80˜7.84 (m, 4H).

[0085]¹³C-NMR: δ 16.2, 17.8, 25.8, 37.0, 55.8, 63.0, 113.5, 116.6,128.2, 128.8, 129.1, 129.1, 133.6, 133.7, 137.3, 138.7, 141.3, 142.7.

EXAMPLE 5:5,9-Di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene

[0086] 1,5-Di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (6.20g, 12.7 mmol) was dissolved in THF (25 ml), and n-BuLi (1.6M solution inhexane/19 ml, 30.5 mmol) was slowly added thereto at −78° C. Theresultant mixture was stirred for 30 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (3.6 g, 14.0 mmol) was addedto the reaction mixture. The reaction mixture was stirred at −78° C. forabout 3 hours and quenched with 1M-HCl solution (20 ml).

[0087] The mixture was slowly warmed up to room temperature andextracted with ether (100 ml). The ether extract was subsequently washedwith distilled water (30 ml), dried over anhydrous sodium sulfate, andfiltered.

[0088] The filtrate was concentrated by evaporation under reducedpressure, and the residue was purified by silica gel columnchromatography to obtain5,9-di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene(7.66 g, 11.6 mmol) (yield: 91%).

[0089]¹H-NMR: δ 1.16 (d, 3H, J=1.1 Hz), 1.35 (s, 3H), 1.47 (s,3H), 1.58(s, 3H), 1.67 (s, 3H), 1.94 (br s, 4H), 2.14 (dd, 1H, J=13.2, 11.9 Hz),2.26 (dd, 1H, J=13.6, 11.5 Hz), 2.73 (d, 1H, J=13.0 Hz), 2.91 (d, 1H,J=12.8 Hz), 3.44 (d, 2H, J=7.8 Hz), 3.72˜3.94 (m, 2H), 4.85 (d, 1H, J9.3 Hz), 4.92 (d, 1H, J=9.6 Hz), 5.02 (br s, 1H), 5.24 (t, 1H, J=7.8Hz), 7.14˜7.33 (m, 5H), 7.40˜7.55 (m, 4H), 7.55˜7.67 (m, 2H), 7.70˜7.87(m, 4H).

[0090]¹³C-NMR: δ 15.9, 16.5, 17.0, 17.7, 25.7, 26.1, 31.7, 37.3, 38.1,39.9, 62.9, 63.4, 117.0, 119.7, 123.2, 123.6, 126.2, 128.7, 128.8,128.9, 129.0, 129.3, 129.5, 131.9, 133.5, 133.7, 134.2, 136.3, 137.4,137.5, 141.2, 145.9.

EXAMPLE 6:1,5,9-Tri(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene

[0091] In methyl alcohol (50 ml), dissolved was 5,9-di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene (7.03 g,10.6 mmol), and LiNbMoO₆ (77 mg, 0.27 mmol) and H₂O₂ (30% aqueoussolution) (3.61 g, 31.8 mmol) were added thereto. The resultant reactionmixture was stirred at room temperature for about 5 hours.

[0092] When the reaction was completed, the reaction mixture was dilutedwith CHCl₃ (100 ml), washed with distilled water (30 ml), dried overanhydrous sodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain1,5,9-tri(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene(5.33 g, 7.7 mmol) (yield: 72%).

[0093]¹H-NMR: δ 1.14 (d, 3H, J=1.2 Hz), 1.32 (s, 3H), 1.34 (d, 3H, J=1.1Hz), 1.58 (s, 3H), 1.67 (s, 3H), 1.92 (br s, 4H), 2.15˜2.36 (m, 2H),2.70˜2.98 (m, 2H), 3.72 (d, 2H, J=7.8 Hz), 3.83 (ddd, 1H, J=10.9, 10.9,3.2 Hz), 3.91 (ddd, 1H, J=10.3, 10.3, 3.3 Hz), 4.89 (d, 1H, J=10.3 Hz),4.93 (d, 1H, J=10.9 Hz), 5.02 (br s, 1H), 5.12 (t, 1H, J=7.8 Hz),7.40˜7.71 (m, 9H), 7.71˜7.93 (m, 6H).

[0094]¹³C-NMR: δ 16.1, 16.4, 16.7, 17.6, 25.6, 26.0, 37.6, 38.1, 39.8,55.7, 62.6, 63.0, 113.7, 117.1, 119.4, 123.6, 128.1, 128.7, 128.9,128.9. 129.1, 129.2, 131.8, 133.5, 133.7, 133.7, 137.3, 137.4, 138.8,140.9, 141.7, 145.8.

EXAMPLE 7-1:Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfide

[0095] In THF (50 ml), dissolved was1,5-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (9.00 g,18.5 mmol). To the solution, n-BuLi (1.6M solution in hexane/23 ml, 37mmol) was slowly added thereto at −78° C. The resultant mixture wasstirred for 20 minutes, and di(4-bromo-3-methyl-2-butenyl sulfide (E)(3.03 g, 9.2 mmol) was added to the reaction mixture. After stirring themixture at the same temperature for 3 hours, aqueous 1M-HCl solution (10ml) was added thereto to quench the reaction.

[0096] The temperature of the reaction mixture was slowly raised to roomtemperature, and ether (100 ml) was added. The resultant mixture wassubsequently washed with aqueous 1M-HCl solution (20 ml×2) and distilledwater (30 ml). The mixture was dried over anhydrous sodium sulfate, andfiltered.

[0097] The filtrate was concentrated by evaporation under reducedpressure, and the residue was purified by silica gel columnchromatography to obtaindi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfide (9.39 g, 8.2 mmol) (yield: 89%).

[0098]¹H-NMR: δ 1.16 (s, 6H), 1.41 (s, 6H), 1.49 (s, 6H), 1.58 (s, 6H),1.68 (s, 6H), 1.95 (br s, 8H), 2.15 (dd, 2H, J=13.0, 11.9 Hz), 2.30 (dd,2H, J=12.6, 11.0 Hz), 2.73 (d, 2H, J=13.0 Hz), 2.86 (d, 2H, J=12.6 Hz),2.95 (d, 4H, J=7.0 Hz), 3.86 (m, 4H), 4.87 (d, 2H, J=10.6 Hz), 4.93 (d,2H, J=9.9 Hz), 5.02 (br s, 2H), 5.18 (t, 2H, J 7.0 Hz), 7.46˜7.58 (m,8H), 7.58˜7.69 (m, 4H), 7.72˜7.90 (m, 8H).

[0099]¹³C-NMR: δ 15.8, 16.4, 16.8, 17.6, 25.6, 26.0, 28.6, 37.3, 38.4,39.8, 62.9, 63.2, 116.8, 119.8, 123.5, 124.3, 128.7, 128.8, 129.0,129.2, 131.9, 133.2, 133.5, 133.6, 137.4, 137.5, 141.1, 146.0.

EXAMPLE 7-2:Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide

[0100] In THF (50 ml), dissolved was1,5-di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene (4.61 g, 11.0 mmol).To the solution, n-BuLi (1.6M solution in hexane/16.5 ml, 26.4 mmol) wasslowly added thereto at −78° C. The resultant mixture was stirred for 20minutes, and di(4-bromo-3-methyl-2-butenyl) sulfide (E) (1.75 g, 5.33mmol) was added to the reaction mixture. After stirring the mixture atthe same temperature for 3 hours, aqueous 1M-HCl solution (10 ml) wasadded thereto to quench the reaction.

[0101] The temperature of the reaction mixture was slowly raised to roomtemperature, and ether (100 ml) was added. The resultant mixture wassubsequently washed with aqueous 1M-HCl solution (20 ml×2) and distilledwater (30 ml). The mixture was dried over anhydrous sodium sulfate, andfiltered.

[0102] The filtrate was concentrated by evaporation under reducedpressure, and the residue was purified by silica gel columnchromatography to obtaindi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide(4.80 g, 4.79 mmol) (yield: 87%).

[0103]¹H-NMR: δ 1.12 (s, 6H), 1.42 (s, 6H), 1.49 (s, 6H), 1.69 (s, 6H),2.03˜2.38 (m, 4H), 2.65˜3.20 (m, 8H), 3.88 (m, 4H), 4.82 (d, 2H, J=10.2Hz), 4.91 (d, 2H, J=9.9 Hz), 5.12 (t, 2H, J=7.3 Hz), 7.53˜7.65 (m, 12H),7.76˜7.84 (m, 8H).

[0104]¹³C-NMR: δ 15.8, 16.8, 17.9, 25.9, 28.5, 37.1, 38.4, 62.8, 63.1,116.9, 119.6, 124.4, 128.8, 128.8, 128.9, 129.1, 133.7, 136.7, 137.1,137.2, 140.4, 140.9, 142.7.

EXAMPLE 8-1:Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone

[0105] In methyl alcohol (20 ml), dissolved wasdi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfide (2.0 g, 1.75 mmol), and LiNbMoO₆ (26 mg, 0.09 mmol) and H₂O₂(30% aqueous solution) (0.99 g, 8.75 mmol) were added thereto. Theresultant reaction mixture was stirred at room temperature for about 5hours.

[0106] When the reaction was completed, the reaction mixture wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtainDi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone (1.48 g, 1.26 mmol) (yield: 72%).

[0107]¹H-NMR: δ 1.15 (s, 6H), 1.41 (s, 6H), 1.58 (s, 6H), 1.61 (s, 6H),1.67 (s, 6H), 1.93 (br s, 8H), 2.17˜2.37 (m, 4H), 2.81 (d, 2H, J=12.3Hz), 2.91 (d, 2H, J=14.1 Hz), 3.56 (d, 4H, J=7.2 Hz), 3.91 (dt, 4H,J_(d)=2.8, J_(t)=9.6 Hz), 4.89 (d, 2H, J=8.8 Hz), 4.92 (d, 2H, J=10.1Hz), 5.01 (br s, 2H), 5.23 (t, 2H, J=7.2 Hz), 7.47˜7.58 (m, 8H),7.58˜7.67 (m, 4H), 7.74˜7.89 (m, 8H).

[0108]¹³C-NMR: δ 16.4, 16.5, 16.6, 17.6, 25.6, 26.0, 37.7, 38.4, 39.7,51.6, 62.5, 62.8, 113.7, 116.9, 118.5, 123.6, 128.7, 128.9, 128.9,129.2, 131.7, 133.5, 133.7, 137.2, 140.8, 140.9, 141.6, 145.8.

EXAMPLE 8-2:Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfone

[0109] In methyl alcohol (50 ml), dissolved wasdi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide(4.54 g, 4.52 mmol), and LiNbMoO₆ (66 mg, 0.23 mmol) and H₂O₂ (30%aqueous solution) (1.54 g, 13.6 mmol) were added thereto. The resultantreaction mixture was stirred at room temperature for about 6 hours.

[0110] When the reaction was completed, the reaction mixture wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtainDi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfone(3.28 g, 3.16 mmol) (yield: 70%).

[0111]¹H-NMR: δ 1.05 (s, 6H), 1.41 (s, 6H), 1.61 (s, 6H), 1.67 (s, 6H),2.17˜2.47 (m, 4H), 2.74˜2.99 (m, 4H), 3.57 (br s, 4H), 3.79˜4.02 (m,4H), 4.86 (d, 2H, J=9.9 Hz), 4.90 (d, 2H, J=10.8 Hz), 5.21 (t, 2H, J=7.5Hz), 7.51˜7.55 (m, 8H), 7.61˜7.66 (m, 4H), 7.76˜7.82 (m, 8H).

[0112]¹³C-NMR: δ 16.6, 16.7, 17.9, 25.9, 37.5, 38.7, 51.6, 62.6, 62.8,113.7, 117.1, 119.4, 128.8, 129.0, 129.0, 129.2, 133.6, 133.8, 137.1,141.0, 141.0, 141.6, 142.7.

EXAMPLE 9-1: 7,7′,11,11′-Tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene

[0113]Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone(1.10 g, 0.94 mmol) was dissolved in a mixture of t-butanol (30 ml) andCCl₄ (30 ml). Minutely pulverized KOH (1.68 g, 30.0 mmol) was addedthereto under argon atmosphere at room temperature. The reaction mixturewas vigorously stirred for 5 hours.

[0114] When the reaction was completed, methylene chloride (60 ml) wasadded thereto to dissolve the mixture, and the resultant solution waswashed with 1M-HCl (20 ml). The combined methylene chloride layer wasdried over anhydrous sodium sulfate, and filtered. The filtrate wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain7,7′,11,11′-tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene(822 mg, 0.74 mmol) (yield: 79%).

[0115]¹H-NMR: δ 1.14 (br s, 6H), 1.33 (s, 6H), 1.58 (s, 6H), 1.60 (s,6H), 1.67 (s, 6H), 1.93 (br s, 8H), 2.16˜2.42 (m, 4H), 2.63˜3.07 (m,4H), 3.68˜4.05 (m, 4H), 4.91 (d, 4H, J=10.6 Hz), 4.98 (br s, 2H),5.69˜5.90 (br s, 2H), 6.08˜6.24 (m, 2H), 7.45˜7.58 (m, 8H), 7.58˜7.70(m, 4H), 7.73˜7.87 (m, 8H).

[0116]¹³C-NMR: δ 16.4, 17.1, 17.7, 24.9, 25.6, 26.1, 28.5, 37.9, 39.8,63.0, 63.6, 116.6, 116.8, 119.9, 123.5, 127.8, 128.7, 128.8, 129.0,129.1, 129.2, 132.0, 133.6, 137.5, 140.6, 141.4, 145.9, 146.1.

EXAMPLE 9-2:2,6,10,15,19,23-Hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene

[0117] Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl)sulfone (1.17 g, 1.13 mmol) was dissolved in a mixture of t-butanol (30ml) and CCl₄ (30 ml). Minutely pulverized potassium hydroxide (KOH/1.90g, 33.8 mmol) was added thereto under argon atmosphere at roomtemperature. The reaction mixture was vigorously stirred for 7 hours.

[0118] When the reaction was completed, methylene chloride (70 ml) wasadded thereto to dissolve the mixture, and the resultant solution waswashed with 1M-HCl (20 ml). The combined methylene chloride layer wasdried over anhydrous sodium sulfate, and filtered. The filtrate wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain2,6,10,15,19,23-hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene(839 mg, 0.87 mmol) (yield: 77%).

[0119]¹H-NMR: δ 1.06 (s, 6H), 1.57 (br s, 6H), 1.61 (s, 6H), 1.66 (s,6H), 2.12˜2.52 (m, 4H), 2.68˜3.07 (m, 4H), 3.64˜4.04 (m, 4H), 4.65˜5.03(m, 4H), 5.69˜5.91 (br d, 2H, J=18.5 Hz), 6.08˜6.26 (m, 2H), 7.43˜7.59(m, 8H), 7.59˜7.70 (m, 4H), 7.73˜7.87 (m, 8H).

EXAMPLE 10-1: Lycopene

[0120] In a mixture of ethanol (20 ml) and benzene (5 ml), dissolved was7,7′,11,11′-tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene(H-1) (682 mg, 0.62 mmol). Sodium ethoxide (NaOEt) (3.35 g, 49.3 mmol)was added thereto under argon atmosphere.

[0121] The reaction mixture was heated under reflux with vigorousstirring for 12 hours.

[0122] When the reaction was completed, benzene (50 ml) was addedthereto to dissolve the mixture, and the resultant solution was washedwith 1M-HCl (10 ml). The combined organic layer was dried over anhydroussodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain lycopene of Chemical Formula2 (260 mg, 0.48 mmol) (yield: 78%).

[0123]¹H-NMR: δ 1.61 (s, 6H), 1.68 (s, 6H), 1.82 (s, 6H), 1.96 (s, 12H),2.11 (br s, 8H), 5.11 (br s, 2H), 5.95 (d, 2H, J=10.8 Hz), 6.18 (d, 2H,J=12.1 Hz), 6.24 (d, 2H, J=14.9 Hz), 6.20˜6.30 (m, 2H), 6.35 (d, 2H,J=14.8 Hz), 6.49 (dd, 2H, J=14.9, 10.8 Hz), 6.63 (dd, 2H, J=14.8, 12.1Hz), 6.55˜6.70 (m, 2H).

[0124]¹³C-NMR: δ 12.8, 12.9, 17.0, 17.7, 25.7, 26.7, 40.2, 123.9, 124.8,125.1, 125.7, 130.1, 131.5, 131.8, 132.6, 135.4, 136.2, 136.5, 137.3,139.5.

[0125] The analytical data of lycopene as above corresponds to NMR dataof trans-lycopene as previously reported (Helv. Chim. Acta 1992, 75,1848-1865).

EXAMPLE 10-2:2,6,10,15,19,23-Hexamethyl-2,4,6,8,10,12,14,16,18,20,22-tetraeicosaundecaene

[0126] In a mixture of ethanol (30 ml) and benzene (5 ml), dissolved was2,6,10,15,19,23-hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene(730 mg, 0.75 mmol). Sodium ethoxide (NaOEt) (4.10 g, 60 3 mmol) wasadded thereto under argon atmosphere.

[0127] The reaction mixture was heated under reflux with vigorousstirring for 12 hours. Then the reaction was completed, benzene (60 ml)was added thereto to dissolve the mixture, and the resultant solutionwas washed with 1M-HCl (10 ml). The combined organic layer was driedover anhydrous sodium sulfate, and filtered. The filtrate wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain2,6,10,15,19,23-hexamethyl-2,4,6,8,10,12,14,16,18,20,22-tetraeicosaundecaene(213 mg, 0.53 mmol) (yield: 71%).

[0128]¹H-NMR: δ 1.82 (s, 12H), 1.97 (s, 12H), 5.94 (d, 2H, J=11 Hz),6.18 (d, 2H,J=12.7 Hz), 6.22 (d, 2H, J=15.3 Hz), 6.16˜6.31 (m, 2H), 6.35(d, 2H, J=14.8 Hz), 6.48 (dd, 2H, J=15.3, 11 Hz), 6.63 (dd, 2H, J=14.8,12.7 Hz), 6.54˜6.67 (m, 2H).

1. An allylic sulfide represented by following Chemical Formula 1:Chemical formula 1

wherein, X is selected from the group consisting of —Cl, —Br, —I,—OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph represents phenylgroup.
 2. A process for preparing an allylic sulfide of Chemical Formula1, which comprises the steps of (a-1) oxidizing isoprene to obtainisoprene monoxide; (b-1) reacting the isoprene monoxide withbenzenethiol to obtain 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A);and (c-1) reacting the compound (A) with a halogenating compound orsulfonylating compound.

In the formulas, X is selected from the group consisting of —Cl, —Br,—I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph representsphenyl group.
 3. A process according to claim 2, Cu(I)-containing saltis used as the catalyst and N,N-dimethylformamide (DMF) as the solventin stage (b-1).
 4. A process according to claim 3, wherein theCu(I)-containing salt is one or more salt(s) selected from the groupconsisting of CuCN, CuI, CuBr and CuCl.
 5. A process for extendingcarbon chain by the use of allylic sulfide of Chemical Formula 1, whichcomprises the steps of (a-2) deprotonating allylic sulfone compound (B),and reacting the resultant compound with allylic sulfide of ChemicalFormula 1 to obtain thio-sulfone compound (C); and (b-2) selectivelyoxidizing the thio-sulfone compound (C) to obtain the correspondingallylic sulfone compound (D).

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃, and Ph represents phenyl group.
 6. A process according toclaim 5, wherein C-5 unit is added by repeating stages (a-2) and (b-2)one or more times by using compound (D) as the starting material.
 7. Aprocess according to claim 5, wherein stage (b-2) is performed by addinghydrogen peroxide solution dropwise to the sulfide compound (C) in thepresence of lithium molybdenate-niobate (LiNbMoO₆) or vanadium oxide(V₂O₅) as a catalyst.
 8. A process for preparing a carotenoid polyenechain compound represented by Chemical formula 2, which comprises thesteps of (a-3) deprotonating the allylic disulfone compound (D), andreacting the resultant compound with not more than 0.5 equivalent ofdiallylic sulfide (E) (wherein, Y is a halogen atom) on the basis of 1equivalent of allylic disulfone compound (D) to obtain allylic sulfidecompound (F); (b-3) selectively oxidizing the allylic sulfide compound(F) to obtain allylic sulfone compound (G); (c-3) subjecting the allylicsulfone compound (G) to Ramberg-Bäklund reaction to givetetra(phenylsulfonyl)-triene compound (H); and (d-3) reacting thecompound (H) with a base.

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, Y is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃ —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃, and Ph represents phenyl group.
 9. A process according toclaim 8, wherein R represents hydrogen or prenyl.
 10. A processaccording to claim 8 or claim 9, wherein the deprotonation step ofdisulfone compound (D) in stage (a-3) is performed by adding not lessthan 2 equivalent of base dropwise to 1 equivalent of allylic disulfonecompound (D) at a temperature of −40° C. or lower.
 11. A processaccording to claim 8 or claim 9, wherein stage (b-3) is performed byadding a mixture of urea-hydrogen peroxide (UHP) and phthalic anhydrideto allylic sulfide compound (F) at a low temperature, or by addinghydrogen peroxide (H₂O₂) solution in the presence of LiNbMoO₆ or V₂O₅ asa catalyst at ambient temperature.
 12. A process according to claim 8 orclaim 9, wherein Ramberg-Bäklund reaction of stage (c-3) is carried outunder nitrogen or argon atmosphere.
 13. A process according to claim 8or claim 9, wherein the base used at stage (d-3) is a metal alkoxide.